tbuckley/cabot-search huggingface dataset:
Persistent Racial/Ethnic Disparities in Cardiology Trainees in the United States
Authors: Abdul Mannan Khan Minhas, Shazib Sagheer, Sardar Hassan Ijaz, Salik Nazir, Muhammad Shahzeb Khan, Syeda Humna Zaidi, Marat Fudim, Fatima Rodriguez, Heather M. Johnson, Salim S. Virani
Journal: Journal of the American College of Cardiology (2022)
Targeting Epstein-Barr virus oncoprotein LMP1-mediated high oxidative stress suppresses EBV lytic reactivation and sensitizes tumors to radiation therapy: Erratum
Authors: Jianmin Hu, Yueshuo Li, Hongde Li, Feng Shi, Longlong Xie, Lin Zhao, Min Tang, Xiangjian Luo, Weihua Jia, Jia Fan, Jian Zhou, Qiang Gao, Shuangjian Qiu, Weizhong Wu, Xin Zhang, Weihua Liao, Ann M. Bode, Ya Cao
Journal: Theranostics (2022)

[This corrects the article DOI: 10.7150/thno.46006.].
mTOR regulates aerobic glycolysis through NEAT1 and nuclear paraspeckle-mediated mechanism in hepatocellular carcinoma
Authors: Hong Zhang, Xiaoyang Su, Stephen K Burley, X F Steven Zheng
Journal: Theranostics (2022)

Background: Hepatocellular Carcinoma (HCC) is a major form of liver cancer and a leading cause of cancer-related death worldwide. New insights into HCC pathobiology and mechanism of drug actions are urgently needed to improve patient outcomes. HCC undergoes metabolic reprogramming of glucose metabolism from respiration to aerobic glycolysis, a phenomenon known as the 'Warburg Effect' that supports rapid cancer cell growth, survival, and invasion. mTOR is known to promote Warburg Effect, but the underlying mechanism(s) remains poorly defined. The aim of this study is to understand the mechanism(s) and significance of mTOR regulation of aerobic glycolysis in HCC. Methods: We profiled mTORC1-dependent long non-coding RNAs (lncRNAs) by RNA-seq of HCC cells treated with rapamycin. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to explore the transcriptional regulation of NEAT1 by mTORC1. [U-13C]-glucose labeling and metabolomic analysis, extracellular acidification Rate (ECAR) by Seahorse XF Analyzer, and glucose uptake assay were used to investigate the role of mTOR-NEAT1-NONO signaling in the regulation of aerobic glycolysis. RNA immunoprecipitation (RIP) and NONO-binding motif scanning were performed to identify the regulatory mechanism of pre-mRNA splicing by mTOR-NEAT1. Myristoylated AKT1 (mAKT1)/NRASV12-driven HCC model developed by hydrodynamic transfection (HDT) was employed to explore the significance of mTOR-NEAT1 signaling in HCC tumorigenesis and mTOR-targeted therapy. Results: mTOR regulates lncRNA transcriptome in HCC and that NEAT1 is a major mTOR transcriptional target. Interestingly, although both NEAT1_1 and NEAT1_2 are down-regulated in HCC, only NEAT1_2 is significantly correlated with poor overall survival of HCC patients. NEAT1_2 is the organizer of nuclear paraspeckles that sequester the RNA-binding proteins NONO and SFPQ. We show that upon oncogenic activation, mTORC1 suppresses NEAT1_2 expression and paraspeckle biogenesis, liberating NONO/SFPQ, which in turn, binds to U5 within the spliceosome, stimulating mRNA splicing and expression of key glycolytic enzymes. This series of actions lead to enhanced glucose transport, aerobic glycolytic flux, lactate production, and HCC growth both in vitro and in vivo. Furthermore, the paraspeckle-mediated mechanism is important for the anticancer action of US FDA-approved drugs rapamycin/temsirolimus. Conclusions: These findings reveal a molecular mechanism by which mTOR promotes the 'Warburg Effect', which is important for the metabolism and development of HCC, and anticancer response of mTOR-targeted therapy.
Endoscopy International Open – recently published
Journal: Endoscopy (2019)

Comment on:The EDGI new take on EDGE: EUS-directed transgastric intervention (EDGI), other than ERCP, for Roux-en-Y gastric bypass anatomy: a multicenter studyEndosc Int Open 2019; 07(10): E1231-E1240DOI: 10.1055/a-0915-2192Comment on:A prospective randomized study of colonoscopy using blue laser imaging and white light imaging in detection and differentiation of colonic polypsEndosc Int Open 2019; 07(10): E1207-E1213DOI: 10.1055/a-0982-3111Comment on:Intraductal temperature-controlled radiofrequency ablation in malignant hilar obstruction: a preliminary study in animals and initial human experienceEndosc Int Open 2019; 07(10): E1293-E1300DOI: 10.1055/a-0970-9005
FcγRIIB regulates autoantibody responses by limiting marginal zone B cell activation
Authors: Ashley N. Barlev, Susan Malkiel, Izumi Kurata-Sato, Annemarie L. Dorjée, Jolien Suurmond, Betty Diamond
Journal: Journal of Clinical Investigation (2022)

FcγRIIB is an inhibitory receptor expressed throughout B cell development. Diminished expression or function is associated with lupus in mice and humans, in particular through an effect on autoantibody production and plasma cell (PC) differentiation. Here, we analyzed the effect of B cell–intrinsic FcγRIIB expression on B cell activation and PC differentiation. Loss of FcγRIIB on B cells in Fcgr2b–conditional KO (Fcgr2b-cKO) mice led to a spontaneous increase in autoantibody titers. This increase was most striking for IgG3, suggestive of increased extrafollicular responses. Marginal zone (MZ) B cells had the highest expression of FcγRIIB in both mice and humans. This high expression of FcγRIIB was linked to increased MZ B cell activation, Erk phosphorylation, and calcium flux in the absence of FcγRIIB triggering. We observed a marked increase in IgG3+ PCs and B cells during extrafollicular PC responses in Fcgr2b-cKO mice. The increased IgG3 response following immunization of Fcgr2b-cKO mice was lost in MZ-deficient Notch2 Fcgr2b–double KO mice. Importantly, patients with systemic lupus erythematosus (SLE) had a decrease in FcγRIIB expression that was strongest in MZ B cells. Thus, we present a model in which high FcγRIIB expression in MZ B cells prevented their hyperactivation and ensuing autoimmunity.
Hematopoietic transcription factor GFI1 promotes anchorage independence by sustaining ERK activity in cancer cells
Authors: Hao Wang, Zhenzhen Lin, Zhe Nian, Wei Zhang, Wenxu Liu, Fei Yan, Zengtuan Xiao, Xia Wang, Zhenfa Zhang, Zhenyi Ma, Zhe Liu
Journal: Journal of Clinical Investigation (2022)

The switch from anchorage-dependent to anchorage-independent growth is essential for epithelial metastasis. The underlying mechanism, however, is not fully understood. In this study, we identified growth factor independent-1 (GFI1), a transcription factor that drives the transition from adherent endothelial cells to suspended hematopoietic cells during hematopoiesis, as a critical regulator of anchorage independence in lung cancer cells. GFI1 elevated the numbers of circulating and lung-infiltrating tumor cells in xenograft models and predicted poor prognosis of patients with lung cancer. Mechanistically, GFI1 inhibited the expression of multiple adhesion molecules and facilitated substrate detachment. Concomitantly, GFI1 reconfigured the chromatin structure of the RASGRP2 gene and increased its expression, causing Rap1 activation and subsequent sustained ERK activation upon detachment, and this led to ERK signaling dependency in tumor cells. Our studies unveiled a mechanism by which carcinoma cells hijacked a hematopoietic factor to gain anchorage independence and suggested that the intervention of ERK signaling may suppress metastasis and improve the therapeutic outcome of patients with GFI1-positive lung cancer.
BRCA1-Dependent and Independent Recruitment of PALB2–BRCA2–RAD51 in the DNA Damage Response and Cancer
Authors: Tzeh Keong Foo, Bing Xia
Journal: Cancer Research (2022)

Abstract The BRCA1–PALB2–BRCA2 axis plays essential roles in the cellular response to DNA double-strand breaks (DSB), maintenance of genome integrity, and suppression of cancer development. Upon DNA damage, BRCA1 is recruited to DSBs, where it facilitates end resection and recruits PALB2 and its associated BRCA2 to load the central recombination enzyme RAD51 to initiate homologous recombination (HR) repair. In recent years, several BRCA1-independent mechanisms of PALB2 recruitment have also been reported. Collectively, these available data illustrate a series of hierarchical, context-dependent, and cooperating mechanisms of PALB2 recruitment that is critical for HR and therapy response either in the presence or absence of BRCA1. Here, we review these BRCA1-dependent and independent mechanisms and their importance in DSB repair, cancer development, and therapy. As BRCA1-mutant cancer cells regain HR function, for which PALB2 is generally required, and become resistant to targeted therapies, such as PARP inhibitors, targeting BRCA1-independent mechanisms of PALB2 recruitment represents a potential new avenue to improve treatment of BRCA1-mutant tumors.
Dissolving “Smart” Pacemaker Design for Temporary Heart Pacing
Authors: Howard D. Larkin
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A Phase II Study of Nivolumab plus Gemcitabine in Patients with Recurrent or Metastatic Nasopharyngeal Carcinoma (KCSG HN17–11)
Authors: Hyun Ae Jung, Keon-Uk Park, Sanghee Cho, Jinyeong Lim, Keun-Wook Lee, Min Hee Hong, Tak Yun, Ho Jung An, Woong-Yang Park, Sergio Pereira, Chan-Young Ock, Bhumsuk Keam
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Although programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors are promising agents for recurrent or metastatic nasopharyngeal carcinoma (NPC), PD-1/PD-L1 inhibitor monotherapy has shown modest efficacy. This study evaluated the efficacy and safety of nivolumab plus gemcitabine in patients with NPC who failed prior platinum-based chemotherapy. Patients and Methods: This is a phase II, multicenter, open-label, single-arm study. Patients with recurrent or metastatic NPC received nivolumab 3 mg/kg and gemcitabine 1,250 mg/m2 every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. To identify potential biomarkers, whole-exome sequencing, whole-transcriptome sequencing, and immune phenotype analysis based on Lunit SCOPE IO, an artificial intelligence–powered spatial tumor-infiltrating lymphocyte analyzer, were performed. Results: Thirty-six patients were enrolled between June 2018 and June 2019. The ORR was 36.1% and disease control rate was 97.2%. With median follow-up of 22.0 months, median PFS was 13.8 months [95% confidence interval (CI), 8.6–16.8 months]. Median OS was not reached, and OS rate at 6 months was 97.0% (95% CI, 80.4%–99.6%). The grade ≥3 treatment-related adverse events were hypertension (2.8%) and anemia (2.8%). In multivariate analysis of mutation of chromatin modifier gene, tumor mutational burden (≥ 2.1 mut/Mb), and somatic copy-number alteration (SCNA) level, the group with high SCNA (&amp;gt; 3 points; HR, 7.0; 95% CI, 1.3–37.9; P = 0.02) had independently associated with poor PFS. Immune phenotype analysis showed that tumors with high proportion of immune-excluded immune phenotype was significantly correlated with poor PFS (HR, 4.4; 95% CI, 1.2–16.2; P = 0.018). Conclusions: Nivolumab plus gemcitabine showed promising efficacy with favorable toxicity profiles in patients with advanced NPC in whom platinum-based combination chemotherapy failed.
Data Errors in Table 1 of Blood Pressure Self-monitoring Trial
Authors: William Feldman
Journal: JAMA (2022)

Katherine L. Tucker, PhD; Sam Mort, PGCert; Ly-Mee Yu, DPhil; Helen Campbell, DPhil; Oliver Rivero-Arias, DPhil; Hannah M. Wilson, MSc; Julie Allen, BSc; Rebecca Band, PhD; Alison Chisholm, PhD; Carole Crawford, MSc; Greig Dougall, PhD; Lazarina Engonidou, MSc; Marloes Franssen, PhD; Marcus Green, BA; Sheila Greenfield, PhD; Lisa Hinton, DPhil; James Hodgkinson, PhD; Layla Lavallee, MSc; Paul Leeson, MB BChir, PhD; Christine McCourt, PhD; Lucy Mackillop, BM, BCh; Jane Sandall, PhD; Mauro Santos, DPhil; Lionel Tarassenko, DPhil; Carmelo Velardo, PhD; Lucy Yardley, PhD; Lucy C. Chappell, MB BChir, PhD; Richard J. McManus, MBBS, PhD; BUMP Investigators; Johanna Cook; Maria Coates; Thomas Gabriel; Stephanie Brann ; Joris De Henau; Sadie Kelly; Dave Watt; David Judge; Luis Castello; Tabitha Wishlade; Helen Price; Eleni Fotaki; Zoe Vowles; Alice Lewin; Hayley Tarft; Julie Wade; Declan Symington; Jessamine Hunt; Maria Slaney; Charlotte Mungeam; Rehan Khan; Amy Thomas; Tabitha Newman; Melanie Gouldbourne; Alexandra Keen; Alice Rossi; Zandile Maseko; David Churchill; Laura Devison; Kayleigh Brooks; Julia Icke; Patrick Bose; Fidelma Lee; Suzanne Scanlon; Joanna Girling; Mark Johnson; Natasha Singh; Carmela Martella; Christine Adamson; Maria Sogo Buaki; Nikki Beadle; Harriet Hickey; Amanda Iriondo-Coysh; Joanna Chilvers; Daisy Duncan; Miriam Bourke; Jenny Myers; Natalie Barry; Heather Glossop; Kimberley Farrant; Clare Waters; Sujatha Thamban; Prudence Jones; Sophia Felippe; Nick Kametas; Polly Kay; Katherine Clark; Rebecca Jarman; Olivia Snowball; Hayley Martin; Osaeloke Osakwe; Bernadette Tilley; Any Barker; Raquel Gonzalez; Asma Khalil; Sophie Robinson; Lisa Canclini; Rebecca Unwin; Katie Morris; Dianne Mellers; Phern Adams ; Lesley Brittain ; Sohpie Dann; Chloe O'Hara; Diane Whitehouse; Bini Ajay; Geraldine Upson; Hannah O'Donnell; Maria Zammit-Mangion; Julie Tebbutt; Lisa Frankland; Danielle Thornton; Kristina Sexton; Rebecca Crowe; Amy Bowers; Joanne Winterbottom
Clinical Protection During the First Omicron Wave in Unvaccinated, Convalescent US Adults—Reply
Authors: Jennifer L. Alejo, Martin A. Makary, Dorry L. Segev
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
AACR Project GENIE: 100,000 Cases and Beyond
Authors: Trevor J. Pugh, Jonathan L. Bell, Jeff P. Bruce, Gary J. Doherty, Matthew Galvin, Michelle F. Green, Haley Hunter-Zinck, Priti Kumari, Michele L. Lenoue-Newton, Marilyn M. Li, James Lindsay, Tali Mazor, Andrea Ovalle, Stephen-John Sammut, Nikolaus Schultz, Thomas V. Yu, Shawn M. Sweeney, Brady Bernard
Journal: Cancer Discovery (2022)

The American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) is an international pan-cancer registry with the goal to inform cancer research and clinical care worldwide. Founded in late 2015, the milestone GENIE 9.1-public release contains data from >110,000 tumors from >100,000 people treated at 19 cancer centers from the United States, Canada, the United Kingdom, France, the Netherlands, and Spain. Here, we demonstrate the use of these real-world data, harmonized through a centralized data resource, to accurately predict enrollment on genome-guided trials, discover driver alterations in rare tumors, and identify cancer types without actionable mutations that could benefit from comprehensive genomic analysis. The extensible data infrastructure and governance framework support additional deep patient phenotyping through biopharmaceutical collaborations and expansion to include new data types such as cell-free DNA sequencing. AACR Project GENIE continues to serve a global precision medicine knowledge base of increasing impact to inform clinical decision-making and bring together cancer researchers internationally.AACR Project GENIE has now accrued data from >110,000 tumors, placing it among the largest repository of publicly available, clinically annotated genomic data in the world. GENIE has emerged as a powerful resource to evaluate genome-guided clinical trial design, uncover drivers of cancer subtypes, and inform real-world use of genomic data. This article is highlighted in the In This Issue feature, p. 2007.
Young Children Increasingly Ingest Melatonin, With Serious Outcomes
Authors: Bridget M. Kuehn
Journal: JAMA (2022)

Growing melatonin use may have contributed to a 530% increase in annual pediatric melatonin ingestions—from 8337 in 2012 to 52 563 in 2021—reported to the American Association of Poison Control Centers’ National Poison Data System, according to a CDC report.
Comorbidities in lichen planus by phenome-wide <i>association</i> study in two biobank population cohorts
Authors: Malin Fromme, Carolin V. Schneider, Christoph Schlapbach, Simone Cazzaniga, Christian Trautwein, Dan J. Rader, Luca Borradori, Pavel Strnad
Journal: British Journal of Dermatology (2022)

Lichen planus (LP) is a relatively frequent mucocutaneous inflammatory disease affecting the skin, skin appendages and mucosae, including oral mucosae, and less frequently the anogenital area, conjunctivae, oesophagus or larynx.To estimate the association of LP, with emphasis on dermatological and gastrointestinal conditions, in two large independent population cohorts.We performed a phenome-wide association study (PheWAS) and examined conditions associated with LP in two unrelated cohorts, i.e. the multicentre, community-based UK Biobank (UKB: 501 381 controls; 1130 LP subjects) and the healthcare-associated Penn Medicine BioBank (PMBB; 42 702 controls; 764 LP subjects). The data were analysed in 2021. The 'PheWAS' R package was used to perform the PheWAS analyses and Bonferroni correction was used to adjust for multiple testing. Odds ratios (ORs) were adjusted for age, sex and body mass index.In the UKB, PheWAS revealed 133 phenome codes (PheCodes) significantly associated with LP and most of them were confirmed in PMBB. Dermatological and digestive PheCodes were the most abundant: 29 and 34 of these disorders, respectively, were significantly overrepresented in LP individuals from both cohorts. The 29 dermatological and 12 oral disorders were often highly enriched, whereas hepatic, gastric, oesophageal and intestinal PheCodes displayed ORs in the range of 1·6-4·5. Several autoimmune disorders also exhibited OR > 5 in both cohorts.PheWAS in two large unrelated cohorts identified previously unknown comorbidities and may support clinical counselling of patients with LP. What is already known about this topic? Lichen planus (LP) is known to affect the skin, skin appendages and mucosae, including oral mucosae, and less frequently the anogenital area, conjunctivae, oesophagus or larynx. What does this study add? Our data provide the most comprehensive collection of associated dermatological, digestive and autoimmune disorders to date. Our findings are expected to be useful for the evaluation and management of patients with LP.
Pharmacogenomic Testing for Next-Step Antidepressant Selection
Authors: Dan V. Iosifescu
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Over-the-Counter Availability of Rescue Inhalers for Asthma—Reply
Authors: William B. Feldman, Jerry Avorn, Aaron S. Kesselheim
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal